Lyme disease caused by the Borrelia species is a growing health concern in many parts of the world. Current treatments for the disease may have side effects, and there is also a need for new therapies that can selectively target the bacteria. Pathogens responsible for Lyme disease include B. burgdorferi, B. afzelii, and B. garinii. In this study, we employed structural docking-based screening to identify potential lead-like inhibitors against the bacterium. We first identified the core essential genome fraction of the bacterium, using 37 strains. Later, we screened a library of lead-like marine microbial metabolites () against the arginine deiminase (ADI) protein of Borrelia garinii. This protein plays a crucial role in the survival of the bacteria, and inhibiting it can kill the bacterium. The prioritized lead compounds demonstrating favorable binding energies and interactions with the active site of ADI were then evaluated for their drug-like and pharmacokinetic parameters to assess their suitability for development as drugs. Results from molecular dynamics simulation (100 ns) and other scoring parameters suggest that the compound CMNPD18759 (common name: aureobasidin; IUPAC name: 2-[(4R,6R)-4,6-dihydroxydecanoyl]oxypropan-2-yl (3S,5R)-3,5-dihydroxydecanoate) holds promise as a potential drug candidate for the treatment of Lyme disease, caused by B. garinii. However, further experimental studies are needed to validate the efficacy and safety of this compound in vivo.

中文翻译：

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筛选海洋微生物代谢物作为有前景的加氏疏螺旋体抑制剂：开发新型莱姆病治疗的结构对接方法

由伯柔氏疏螺旋体引起的莱姆病在世界许多地区日益成为人们关注的健康问题。目前对该疾病的治疗可能有副作用，并且还需要能够选择性地针对细菌的新疗法。引起莱姆病的病原体包括伯氏疏螺旋体、阿夫泽勒疏螺旋体和加里尼疏螺旋体。在这项研究中，我们采用基于结构对接的筛选来识别潜在的针对该细菌的类先导抑制剂。我们首先使用 37 个菌株鉴定了该细菌的核心必需基因组部分。后来，我们筛选了一个类铅海洋微生物代谢物库（)对抗加氏疏螺旋体 ( Borrelia garinii ) 的精氨酸脱亚胺酶 (ADI) 蛋白。这种蛋白质对于细菌的生存起着至关重要的作用，抑制它可以杀死细菌。然后，对表现出有利的结合能以及与 ADI 活性位点相互作用的优先先导化合物的类药和药代动力学参数进行评估，以评估其作为药物开发的适合性。分子动力学模拟（100 ns）和其他评分参数的结果表明化合物CMNPD18759（通用名：aureobasidin；IUPAC名称：2-[（4 R ,6 R）-4,6-二羟基癸酰基]oxypropan-2-yl（ 3 S ,5 R )-3,5-二羟基癸酸酯）有望成为治疗由B. garinii引起的莱姆病的潜在候选药物。然而，还需要进一步的实验研究来验证该化合物在体内的功效和安全性。